bs148h 27 September 2007Read: Text pgs 818-819, ch 40 & 41

• form & function• tubes• germ Layers • tissues• epithelium• connective• muscle & nerve• skeletal muscle• Eat Food!• teeth & guts• glucose regulation; negative feedback• fat regulation

http://www.madsci.org/~lynn/VH/transverse.html

(Form Follows Function) - constrained by physical lawsin particular environments.

Multicellular organisms areorganisms are big, aggregated lineages (clones) of cellscells(plus various symbionts, parasites, mutants etc.).

Each cell is plasma-membrane bound aqueous system, with homeostatic mechanismshomeostatic mechanisms to maintain stasis (or growth) by regulating exchange: energy, nutrients ‘raw materials’ etc IN

& wastes, hormones, ‘products’ etc OUT

Diffusion through tissuesis very slow & inefficient.

Large animals are masses of tubesLarge animals are masses of tubesw/ ↑ surface/vol & ↓ diffusion dist.

Bulk flow through tubes (gut, lungs, arteries & veins, lymph etc)minimizes diffusion distances.

In mammals the the coelomcoelom is divided by the diaphragm into theperitoneal cavityperitoneal cavity – contains stomach, intestines, liverthoracic cavitythoracic cavity – subdivided into

pleural cavities – lungspericardial cavity - heart

The endoderm gut tubegut tube passes through the mesoderm coeloemcoeloem

http://www.madsci.org/~lynn/VH/transverse.html

are a tube

The vertebrate body is a tube within a tubeThe vertebrate body is a tube within a tube

The cells of the embryo differentiate into 3 germ layers3 germ layers

{see ch 47}

http://stemcells.nih.gov/info/scireport/chapter1.asp

Skin, Neural tissue

Adrenal medulla, Pituitary gland

Connective tissue of the head and face,

Eyes, ears

Bone marrow (blood), Adrenal cortex,

Lymphatic tissueSkeletal, smooth, and cardiac

muscle, neural crest Connective tissues (including

bone, cartilage)Urogenital system,

Heart & blood vessels

Thymus, Thyroid, parathyroid glands, Larynx,

trachea, lungUrinary bladder, vagina, urethra

Gastrointestinal (GI) organs (liver, pancreas)

Lining of the GI tract & the respiratory tract

Animals are multicellular organisms with their specialized cells grouped into tissuestissues. TissuesTissues are integrated groups of cells with a common structure and function. Combinations of various tissues make up functional units called organsorgans,

and groups of organs that work together form organ systemsorgan systemsAll organs are made of the four basic tissue types. All organs are made of the four basic tissue types.

http://mindquest.net/biology/histology/index.htmlEpithelial tissueEpithelial tissue is derived from all 3 germ layers;- covers the outside of the body; lines internal organs & cavities;secrete material (e.g. glands), or absorb material (e.g. intestine).

Connective tissueConnective tissue (mainly ectoderm & mesoderm) connects body parts, Many subtypes of connective tissue, including bone, cartilage, ligaments & tendons, adipose (fat) tissue, areolar (loose irregular) connective tissue, and blood (connective tissue because it derives from bone marrow).

Nerve cells,Nerve cells, known as neurons, (from ectoderm) are specialized for conducting electrical signals in the body.

Muscle cellsMuscle cells (from mesoderm) have the ability to contract/shorten. This allows muscle tissue to function for providing movement …There are three subtypes of muscle tissue:

skeletal muscle, smooth muscle, and cardiac (heart) muscle.

Epithelial tissueEpithelial tissue lines all body surfaces… the mouth, esophagus, uterus and vagina,

ducts of the pancreas and liver, urethra and ureters,blood vessels (where it is called endothelium), tubules of the kidney, air sacs (alveoli) of the lungs ...

Epithelial tissueEpithelial tissue is derived from all three germ layers; functions to protectprotect surfaces (eg skin), secretesecrete material (eg glands), absorbabsorb material (eg intestine).

http://mindquest.net/biology/histology/epithelial-tissue.html

Epithelial tissue is classified according to

(1) the shapeshape of the outermost cell layer squamoussquamous [flat]: [flat]: linings - diffusioncuboidalcuboidal: : glands & tubules - transportcolumnar:columnar: linings – secretion & absorptionor transitional, {discrete categorization is an ‘ideal’}

(2) whether or not the tissue is one layer thickone layer thick (simplesimple): lungs & capillaries

or multiple layersmultiple layers (stratifiedstratified): skin, mouthor ‘pseudostratifiedpseudostratified’: glands & mucous membranesand (3) whether or not the cells are

ciliatedciliatedor secretesecrete (glandular, ex: goblet cell) …

http://www.mc.vanderbilt.edu/histo/BasicTissue/Epith.Definition.html

Characterisitics of epithelial cellsepithelial cells:They are contiguous (connected w/ tight junctions). Epithelia are avascular … blood vessels do not penetrate

up between these cells … {ex: blood-brain barrier}Unlike muscle and connective tissue, they can be derived from

any of the three embryologic germ layers (endoderm, mesoderm, ectodermendoderm, mesoderm, ectoderm). Rapid replacementRapid replacement: stomach epithelium replaced ~2-3 days; epidermis ~2 weeks; A major cytoskeletal component of skin epithelia is the filament called keratinkeratin{the main component of: mammal hair, reptile scales, bird feathers, claws (including nails and hooves), horn (but not antlers), & the enamel of the teeth }.

see Fig 6.31

… rest on an extracellularextracellular matrixmatrix which they produce … the basement membranebasement membrane. … basement membranebasement membrane …

is a thin sheet of collagencollagen{dense connective tissue Fig 40.5}

Cancer biology: Breaking and enteringCancer biology: Breaking and enteringGenes Dev. doi:10.1101/gad.1451806 (2006)To spread, or metastasize, cancer cells must escape from their site of origin. Doing so requires crossing the basement membrane, a barrier of connective tissue.S Weiss and colleagues have identified three enzymes that allow tumors to

degrade proteins in the basement membrane, allowing cancer cells to escape. Knowing the enzymes ... could enable future cancer therapies to target this process.

Glandular epithelia, absorb or secrete chemical solutions. Glandular epithelia, absorb or secrete chemical solutions. EndoEndocrinecrine glandular epithelia secrete hormones into the bloodinto the blood (ch 45)ExoExocrinecrine glands channel product to epithelial surfaceto epithelial surface.

ex: tear, sweat and sebaceous glands to skin; liver to gut.Glandular epithelia that line the digestive & respiratory tracts form mucous membranemucous membrane;

they secrete a slimy solution called mucusmucus that lubricates the surface. The epithelium of our respiratory tract has beating cilia The epithelium of our respiratory tract has beating cilia

that move the film of mucus along the surface: helps keep our lungs clean by trapping dust, ‘germs’ and other particles and sweeping them back up the trachea (windpipe) – to esophagus.

water-soluable

Vertebrate glands (ch 45) develop from invaginated epithelium

The lipidlipid {water insoluable} component of milk is released in an envelope of plasma membrane by apocrineapocrine secretion.{homogenization breaks up large globules}

The proteinprotein {water soluable} component of milk is released into solution by merocrinemerocrine secretion.

http://courseweb.edteched.uottawa.ca/medicine-histology/English/Reproduction/Mammary/Mammary_repro.htm

In the inactive mammary glandmammary gland, the glandular elements consist only of ducts:lined by cuboidal or columnar epithelium ...

Dramatic changes in the mammary gland occur during pregnancyduring pregnancy. Ducts proliferate and secretory alveoli sprout from them. Alveoli are collections of cuboidal or columnar epithelial cells

that become active milk-secreting structures.

During the menstrual cycleDuring the menstrual cycleslight development of secretory alveoli may begin ...

… an increasing number of menstrual cycles increases the stimulation of breast ductal epithelial cells and one’s risk of breast cancer.

… the risk for breast cancer is associated the risk for breast cancer is associated with lifetime exposure to estrogen.with lifetime exposure to estrogen.

see: http://www.cancer.gov/cancertopics/factsheet/Risk/oral-contraceptives

Menstrual and reproductive factors and endometrial cancer risk ...Xu et al. 2004. Int J Cancer 108(4):613-9.

Connective Tissue Connective Tissue derives from embryonic mesoderm,functions mainly to bind and support other tissues.

… has a sparse population of cells scattered through an extracellular matrix. The major types of connective tissue in vertebrates are

Loose connective tissueLoose connective tissue (Fig 40.5)(including Adipose tissueAdipose tissue = fat)

Fibrous (dense) connective tissueFibrous (dense) connective tissueregularregular-- ligaments & tendonsirregularirregular – sheathing membranes

CartilageCartilageBone Bone BloodBlood

Fibrous connective tissueFibrous connective tissue is dense, due to its large numbers of collagenouscollagenous fibersfibers.

The “unhappy triad” is where the ACL is torn at the same time as the MCLand the lateral meniscus (one of the shock absorbing cartilagescartilages in the knee).

… articulararticular (meniscus) cartilage(meniscus) cartilagelining the bones of your knee jointhas limited ability to heal itself.has limited ability to heal itself.Blood capillaries do not penetrate the joint capsule. {similar to ‘the blood-brain barrier’} . Synovial fluid, secreted bysynovium (membranes), lubricates the joint andcarries nutrients to the cartilage.

CartilageCartilage has collagenouscollagenous fibersfibersembedded in a rubbery matrix of chondroitinchondroitin sulfatesulfate, a protein-carbohydrate complex.

… secreted by cells called chondrocyteschondrocytes.

In tendonstendons, which attach muscles to bones, and in ligamentsligaments, which join bones together at joints.the fibers are organized into parallel bundles …

Rheumatic diseases are connective tissue diseases. Rheumatic diseases are connective tissue diseases. Arthritis means joint inflammationArthritis means joint inflammation.… arthritis is a kind of rheumatic disease.Osteoarthritis,Osteoarthritis, the most common type, affects cartilageaffects cartilage,

the tissue that cushions the ends of the bones within the joints.

Rheumatoid arthritis is an autoimmune diseaseRheumatoid arthritis is an autoimmune disease… the immune system attacks a person's own synovium,

the tissue inside the joint capsule. {one type of antibody attacks the ‘tail’ of another type}

http://en.wikipedia.org/wiki/Rheumatoid_arthritisThe cause of RA is unknown ...the "mistaken identity" theory suggests that

an offending organism causes an immune response that leaves behind antibodies specific to that organism.

They begin an immune attack against the synovium, because a molecule in the synovium "looks like" one on the offending organism.

90% of patients with RA have the cluster of markers known as the HLA-DR4/DR1 cluster, whereas only 40% of controls do.

Thus, in theory, RA requires susceptibility to the diseasethrough genetic endowment and an infectious event that triggers an autoimmune response.

BoneBone is an extracellular mineralized connective tissue (from mesoderm). Bone-forming cells called osteoblastsosteoblasts deposit a matrix of collagen.collagen.Calcium, magnesium, and phosphate ions combine

and harden within the matrix into the mineral hydroxyapatitehydroxyapatite – rigid but brittle.

The structure of hard mammalian bone consists of repeating units called osteonsosteons ((or HaversianHaversian systems). systems).

Each osteon has concentric layers of the mineralized matrix, which are deposited around a central canal containing blood vessels and nerves that service the bone.

Mature osteocytesosteocytes maintain, remodel and repair mineral bone.

Optimization of bone growth and remodeling in response to loadingbone growth and remodeling in response to loading ...Lieberman et al. 2003 J Exp Biol. 206:3125-38limb bones initially optimize {growth} responses to loading ... In juveniles, exercise induces higher rates of {remodeling} ... {but less so in adults}

BloodBlood functions differently from other connective tissues (mesoderm) but it has an extensive extracellular matrix: a liquid called plasmaplasma,

consisting of water, salts, and a variety of dissolved proteins. Suspended in the plasma are two classes of blood cells, erythrocyteserythrocytes (red blood cells) and leukocytesleukocytes (white blood cells), and cell fragments called plateletsplatelets. Blood will be discussed later (Chapters 42, 43 & 44).

Nervous tissueNervous tissue (from ectoderm) senses stimuli and transmits signals from one part of the animal to another,

& stores memories. The functional unit of nervous tissue

is the neuron, or nerve cell, Discussed later in ch 48

ArcheoArcheo--Cell Biology: Carbon Dating Is Not Just for Pots and DinosaursCell Biology: Carbon Dating Is Not Just for Pots and DinosaursP Arlotta & JD Macklis 2005 Cell 122: 4-6. In this issue of Cell, Spalding et al. (2005) describe a clever strategy

for birth dating human cells in vivo, based on incorporation of 14C during a peak in atmospheric levelsresulting from above-ground nuclear arms testing in the 1950s.

The amount of 14C in neurons of the human cerebral cortex corresponds to the amount in the atmosphere at the time of birth ...

occipital neurons are as old as the individualoccipital neurons are as old as the individual

MuscleMuscle tissue (from mesoderm) is composed of long cells called muscle fibers that are capable of contracting when stimulated by nerve impulses. Arranged in parallel within the cytoplasm of muscle fibers

are large numbers of myofibrils made of the contractile proteins actinactin and myosinmyosin. Recall actin in eukaryotic cytoskeleton (see ch 6)

Smooth muscleSmooth muscle is found throughout animals.In vert’s – ‘visceral’ muscle, sheets surround

larger blood vessels and bronchia, gut, iris of eye. Not striated (lined up)

Not ‘voluntary;’ spontaneous waves in gut;

Skeletal muscleSkeletal muscle is usually attached to tendons & bonesat origin & insertion; antagonists flex & extend.

Lined up in orderly, multinucleate myofibrils – ‘striated.’‘Voluntary;’ excited at neuromuscular synaptic junctions

Cardiac (heart) muscleCardiac (heart) muscle‘striated’ but single cells (& nuclei) linked by gap junctionsinto single functioning myocardiumSpecialized ‘autogenic’ cells maintain rhythmic contractions;

modified by sympathetic (+) and parasympathetic (-) nerves

Each skeletal muscleskeletal muscle is an nested hierarchy of filaments.

Somatic motor neurons release acetylcholine Achacetylcholine Ach (blocked by Botox)

ContractionContraction:

Sliding filament mechanism Sliding filament mechanism (see ch 49)

Ach depolarizes muscle ... starting the power cycle

Power cyclePower cycle (see Fig 49.30);

(a) myosin splits ATP

(b) cross-bridges w/ actin,

(c) myosin head bends (power stroke -rowing)

(d) new ATP releases bridge, straightens →(a)

Rigor mortis – no ATP to break bridges

actin Z bands get closer, Sarcomeres shortenmuscle contracts

Another toxin used for its muscle relaxant properties is botulinumbotulinum toxintoxin, from bacteria Clostridium botulinum

The toxin gets into motor nerve terminals and prevents the release of acetylcholineprevents the release of acetylcholine{presynaptic vesicle can’t fuse w/ membrane}

… botulinum toxin is often regarded as one of the most toxic substances known …

However, its specificity and irreversibilityhave been useful …

When BotoxBotox is injected into a muscle, it blocks the nerve impulse from reaching that area, and as a result, the muscle weakens.

As the muscle weakens, the skin overlying the muscle relaxes and the wrinkles in the skin gradually soften and often disappear.

http://ci.mond.org/9522/952214.htmlFrom venoms to toxins to drugs:From venoms to toxins to drugs:Toxins have been used to elucidate

physiological mechanisms; the pure alkaloid, tubocurarinetubocurarine,

isolated from the arrow poison curarecurare, has been used as a muscle relaxant to accompany general anaesthetic.

{blocks Ach binding at neuromuscular junction}

Essentially We Have Two Essentially We Have Two FibreFibre Types:Types:FastFast--twitch (Type 2)twitch (Type 2) & SlowSlow--twitch (Type 1)twitch (Type 1)High intensity, anaerobic, short-burst activity, engages the fastfast--twitchtwitch fibres,

which are lighter in coloring than slow-twitch fibresdue to the low levels of myoglobin (stores oxygen for use in cell respiration) and mitochondria they possess – quickly fatiguequickly fatigue.

SlowSlow--twitchtwitch fibres, on the other hand, possess more mitochondria and myoglobin, and are red in coloring as a result. Fatigue resistanceFatigue resistance, at the expense of fast rate force production, is the hallmark of these fibres.

The average person has about 50% slow & 50% fast fibres in locomotory muscles. You can almost guarantee that newly crowned 100-meter Olympic sprint champion

Justin Gatlin has around 80% fast twitch fibres in his quadriceps muscles. {the proportions change with age and can be changed with training}

To simplify things somewhat, a nice analogy can be used to explain the various actions of these two fibre types.

ChickensChickens, like us, have both fast and slow-twitch fibres: their darker (red) meat(red) meat is composed of slow-twitch fibres,and the white meatwhite meat of fast-twitch fibres.

Chickens use their legs (red meatred meat) for walking and standing for large periods of time, while their wings (white meatwhite meat) are used for brief bursts of activity.

ACTN3ACTN3 genotype is associated with human elite athletic performance. genotype is associated with human elite athletic performance. Yang, N. et al. Am. J. Hum. Genet. 73, 627–631 (2003). ArticleThere is increasing evidence for strong genetic influences on athletic performance

and for an evolutionary "trade-off" between ... speed and endurance ... ... the skeletal-muscle actin-binding protein αα--actininactinin--3 is specifically expressed in 3 is specifically expressed in

fastfast--twitch (type 2) twitch (type 2) myofibersmyofibers responsible for generating force at high velocityresponsible for generating force at high velocity... is absent in 18% of healthy white individuals because of homozygosity for

a common stop-codon polymorphism in the ACTN3 gene, R577X. {allele R577 codes for R577 codes for αα--actininactinin--3; 3; R577XR577X is a defective ACTN3, homozygote R577XXR577XX results in no no αα--actininactinin--33}

... highly significant associations between ACTN3 genotype and athletic performance. Both male and female elite sprint athletessprint athletes

have significantly higher frequencies of the have significantly higher frequencies of the R577 allele than do controls. than do controls. The differential effects in sprint and endurance athletes suggests that

the R577 R577 vs R577XR577X polymorphism {at the ACTN3 locus} may have been maintained in the human population by balancing natural selection.

Loss of ACTN3 gene function alters mouse muscle metabolism and shows evidence of positive selection in humans

D.G. MacArthur et al. Nature Genetics 39, 1261 - 1265 (2007)

All animals eat other organismsAll animals eat other organismsdead or alive, whole or by the patty

An adequate diet must satisfy three nutritional needs: 1 fuelfuel (chemical energy) for all cellular work of the body;

{empty calories in junk food serve this purpose OK}2 the organic raw materials animals use in biosynthesis;

Given a source of organic carbonorganic carbon (such as sugar) & organic nitrogenorganic nitrogen (usually amino acids in protein), animals can fabricate a great variety of organic molecules- carbohydrates, proteins, and lipids;

3 essential nutrientsessential nutrients substances that the animal cannot make for itself from any raw material and must obtain in food in prefabricated form: essential amino acids (8 or 9, see http://en.wikipedia.org/wiki/Essential_amino_acid )fatty acids (omega-3 & -6: http://en.wikipedia.org/wiki/Essential_fatty_acids ) vitamins, and minerals (Table 41)

complementary foodscomplementary foods{not complimentary}

balance essential nutrientsacross plant foods

Teeth and Guts Teeth and Guts are great indicators of diet

The vestigiality of the human vermiform appendix

... as is the number of copies of the gene coding for the salivary enzyme amlayse, which digests complex starches into simple sugars ...

news@naturenews@nature Ewen Callaway, Published online: 9 September 2007;The gene that makes your mouth waterAbility to digest starch could have spurred human evolution.Compared with chimpanzees, humans boast many more copies of the gene that makes

salivary amylase – a saliva enzyme that breaks down starch into digestible sugars.And carbohydrate-loving societies carry more copies of the gene

than those that follow low-carbohydrate diets, says a new study in Nature Genetics1.

When fewer calories are taken in than are expended ... the body expends liver glycogen, then muscle glycogen and fat. {released as glucose, into blood}

Blood glucose levels are regulated by Blood glucose levels are regulated by complementary complementary ‘‘pushpush--pullpull’’negative feedback systems: negative feedback systems:

insulininsulin pulls high blood glucose downglucagonglucagon pushes low glucose up

(Figs 41.3 & 45.12) ‘set point’Type 1 diabetesType 1 diabetes mellitus:

loss of insulin-producing beta cells;autoimmune, juvenile onset

Type 2 diabetesType 2 diabetes is often due to reduced responsiveness to insulin, associated w/ obesity in adults

Glucose Regulation as an Example of Glucose Regulation as an Example of {push-pull –FB} HomeostasisHomeostasisWhen an animal takes in more calories than it needs ...

the liver and muscle cells store energy in the form of glycogenglycogen, a polymer made up of many glucoseglucose units.

If the body′s glycogen depots are full the excess is usually stored as fatfat.

The complexity of weight control in humans is evident from studies of the hormone leptinleptin, a long–term appetite regulator in mammals.

Leptin is produced by adipose (fat) cells. As adipose tissue increases,

leptin levels in the blood rise, which normally suppresses appetite.

Loss of body fat decreases leptin levels, signaling the brain to increase appetite.

Over the long term, homeostatic mechanisms, involving hormones in feedback circuits to a a ““satiety centersatiety center”” in the brainin the braincontrol the body′s storage and metabolism of fatfat.

Both of these mice have a defect in a gene called obese (ob). This mutation results in a marked increase in the amount of fat.

Administration of the protein encoded by the ob gene, called leptinleptin, {Greek –”thin”}reduced the body weight of the ob mice. {In obese humans, defective receptor}

Body fat mass, Body fat mass, leptinleptin and puberty.and puberty.Kiess et al. 2000. J. Ped. Endo. & Metab 13:717-722.

By modulating the hypothalamo-pituitary-gonadal axis both directly and indirectly, leptinleptin may thus serve as the signal from fat to the brain may thus serve as the signal from fat to the brain about the adequacy of fat stores for pubertal development and reproduction.

Normal leptin secretion is necessary for normal reproductive function to proceed and leptin may be a signal allowing for … progression toward puberty.

Role of Role of leptinleptin in reproductionin reproduction..Bajari et al. CURRENT OPINION IN LIPIDOLOGY 15 (3): 315-319 JUN 2004 The development of therapeutic agents against obesity must consider

the consequences of treatment on the bioactivity of leptinin the context of growth, glucose homeostasis, and last but not least, fertility.

Mastering Leptin explains how we can conquer the obesity epidemic in America. Finally the mysteries of the hormone leptin have been unlocked,

opening the door for permanent weight loss { too good to be true?}